Although hypothalamic neurohormones were originally identified on the basis of their ability to influence hormone release from the target cells, it is at present clear that these agents are involved in the control of several biological processes that include cell proliferation and differentiation as well as hyperplasia and neoplastic transformation. Hypothalamic neurohormones bind specific receptors belonging to the G-protein-coupled receptor superfamily to generate intracellular effectors, in particular cAMP and calcium. Several in vivo and in vitro studies suggest the presence of functional and/or structural alterations in the receptor/effector molecules involved in the transduction of hypothalamic neurohormone action in the pituitary. The present study reports the frequent presence in pituitary tumors of cellular alterations that result in amplification of stimulatory signals, particularly activation of the cAMP-dependent pathway, and reduction of inhibitory inputs, both events having possible implications in tumor formation and/or progression.